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PloS One 2019Antibodies are essential to functional immunity, yet the epitopes targeted by antibody repertoires remain largely uncharacterized. To aid in characterization, we...
Antibodies are essential to functional immunity, yet the epitopes targeted by antibody repertoires remain largely uncharacterized. To aid in characterization, we developed a generalizable strategy to predict antibody-binding epitopes within individual proteins and entire proteomes. Specifically, we selected antibody-binding peptides for 273 distinct sera out of a random library and identified the peptides using next-generation sequencing. To predict antibody-binding epitopes and the antigens from which these epitopes were derived, we tiled the sequences of candidate antigens into short overlapping subsequences of length k (k-mers). We used the enrichment over background of these k-mers in the antibody-binding peptide dataset to predict antibody-binding epitopes. As a positive control, we used this approach, termed K-mer Tiling of Protein Epitopes (K-TOPE), to predict epitopes targeted by monoclonal and polyclonal antibodies of well-characterized specificity, accurately recovering their known epitopes. K-TOPE characterized a commonly targeted antigen from Rhinovirus A, predicting four epitopes recognized by antibodies present in 87% of sera (n = 250). An analysis of 2,908 proteins from 400 viral taxa that infect humans predicted seven enterovirus epitopes and five Epstein-Barr virus epitopes recognized by >30% of specimens. Analysis of Staphylococcus and Streptococcus proteomes similarly predicted 22 epitopes recognized by >30% of specimens. Twelve of these common viral and bacterial epitopes agreed with previously mapped epitopes with p-values < 0.05. Additionally, we predicted 30 HSV2-specific epitopes that were 100% specific against HSV1 in novel and previously reported antigens. Experimentally validating these candidate epitopes could help identify diagnostic biomarkers, vaccine components, and therapeutic targets. The K-TOPE approach thus provides a powerful new tool to elucidate the organisms, antigens, and epitopes targeted by human antibody repertoires.
Topics: Adolescent; Adult; Aged; Algorithms; Antibodies; Antigens, Bacterial; Antigens, Viral; Child; Enterovirus; Epitopes; Humans; Middle Aged; Proteome; Proteomics; Sequence Analysis, Protein; Staphylococcus; Streptococcus
PubMed: 31490930
DOI: 10.1371/journal.pone.0217668 -
The Journal of General Virology Nov 2011HeLa cells are used to study the life cycles of many different viruses, including the human rhinoviruses (HRV) in the family Picornaviridae. Although the natural targets... (Comparative Study)
Comparative Study
HeLa cells are used to study the life cycles of many different viruses, including the human rhinoviruses (HRV) in the family Picornaviridae. Although the natural targets of HRV are human bronchial epithelial cells (hBE), it is generally more difficult to obtain and maintain the relevant primary cell cultures, relative to HeLa cells. Given that the HRV are now identified as a major cause of human asthma exacerbations, it becomes important to document how much of the virus biology learned from HeLa cells is common also to natural primary cells. When compared directly in matched infections using A01a virus, the kinetics of RNA replication, the synthesis and processing of viral proteins and the general subcellular localization of key non-structural proteins were resembled in hBE and HeLa cells. Viral-induced shutoff of host cell processes (e.g. nucleo-cytoplasmic trafficking) was also comparable.
Topics: Cells, Cultured; Epithelial Cells; Humans; Rhinovirus; Virus Cultivation; Virus Replication
PubMed: 21752966
DOI: 10.1099/vir.0.031302-0 -
American Journal of Respiratory and... Oct 2017Allergic inflammation has been linked to increased susceptibility to viral illnesses, but it is unclear whether this association is causal.
RATIONALE
Allergic inflammation has been linked to increased susceptibility to viral illnesses, but it is unclear whether this association is causal.
OBJECTIVES
To test whether omalizumab treatment to reduce IgE would shorten the frequency and duration of rhinovirus (RV) illnesses in children with allergic asthma.
METHODS
In the PROSE (Preventative Omalizumab or Step-up Therapy for Severe Fall Exacerbations) study, we examined children with allergic asthma (aged 6-17 yr; n = 478) from low-income census tracts in eight U.S. cities, and we analyzed virology for the groups randomized to treatment with guidelines-based asthma care (n = 89) or add-on omalizumab (n = 259). Weekly nasal mucus samples were analyzed for RVs, and respiratory symptoms and asthma exacerbations were recorded over a 90-day period during the fall seasons of 2012 or 2013. Adjusted illness rates (illnesses per sample) by treatment arm were calculated using Poisson regression.
MEASUREMENTS AND MAIN RESULTS
RVs were detected in 97 (57%) of 171 exacerbation samples and 2,150 (36%) of 5,959 nonexacerbation samples (OR, 2.32; P < 0.001). Exacerbations were significantly associated with detection of rhinovirus C (OR, 2.85; P < 0.001) and rhinovirus A (OR, 2.92; P < 0.001), as well as, to a lesser extent, rhinovirus B (OR, 1.98; P = 0.019). Omalizumab decreased the duration of RV infection (11.2 d vs. 12.4 d; P = 0.03) and reduced peak RV shedding by 0.4 log units (95% confidence interval, -0.77 to -0.02; P = 0.04). Finally, omalizumab decreased the frequency of RV illnesses (risk ratio, 0.64; 95% confidence interval, 0.49-0.84).
CONCLUSIONS
In children with allergic asthma, treatment with omalizumab decreased the duration of RV infections, viral shedding, and the risk of RV illnesses. These findings provide direct evidence that blocking IgE decreases susceptibility to RV infections and illness. Clinical trial registered with www.clinicaltrials.gov (NCT01430403).
Topics: Adolescent; Anti-Asthmatic Agents; Asthma; Child; Female; Humans; Male; Omalizumab; Rhinovirus; United States; Virus Diseases
PubMed: 28608756
DOI: 10.1164/rccm.201701-0120OC -
The Journal of Infectious Diseases Jan 2018Little is known about T cells that respond to human rhinovirus in vivo, due to timing of infection, viral diversity, and complex T-cell specificities. We tracked... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Little is known about T cells that respond to human rhinovirus in vivo, due to timing of infection, viral diversity, and complex T-cell specificities. We tracked circulating CD4+ T cells with identical epitope specificities that responded to intranasal challenge with rhinovirus (RV)-A39, and we assessed T-cell signatures in the nose.
METHODS
Cells were monitored using a mixture of 2 capsid-specific major histocompatibility complex II tetramers over a 7-week period, before and after RV-A39 challenge, in 16 human leukocyte antigen-DR4+ subjects who participated in a trial of Bifidobacterium lactis (Bl-04) supplementation.
RESULTS
Pre-existing tetramer+ T cells were linked to delayed viral shedding, enriched for activated CCR5+ Th1 effectors, and included a minor interleukin-21+ T follicular helper cell subset. After RV challenge, expansion and activation of virus-specific CCR5+ Th1 effectors was restricted to subjects who had a rise in neutralizing antibodies, and tetramer-negative CCR5+ effector memory types were comodulated. In the nose, CXCR3-CCR5+ T cells present during acute infection were activated effector memory type, whereas CXCR3+ cells were central memory type, and cognate chemokine ligands were elevated over baseline. Probiotic had no T-cell effects.
CONCLUSIONS
We conclude that virus-specific CCR5+ effector memory CD4+ T cells primed by previous exposure to related viruses contribute to the control of rhinovirus.
Topics: Adolescent; Adult; Blood; Cell Tracking; Enterovirus; Enterovirus Infections; Female; Humans; Immunologic Memory; Male; Middle Aged; Nasal Mucosa; Receptors, CCR5; Th1 Cells; Young Adult
PubMed: 29309618
DOI: 10.1093/infdis/jix514 -
PloS One 2013Human rhinoviruses (HRVs), in the Enterovirus genus within the family Picornaviridae, are a highly prevalent cause of acute respiratory infection (ARI). Enteroviruses...
Human rhinoviruses (HRVs), in the Enterovirus genus within the family Picornaviridae, are a highly prevalent cause of acute respiratory infection (ARI). Enteroviruses are genetically highly variable, and recombination between serotypes is known to be a major contribution to their diversity. Recently it was reported that recombination events in HRVs cause the diversity of HRV-C. This study analyzed parts of the viral genes spanning the 5' non- coding region (NCR) through to the viral protein (VP) encoding sequences of 105 HRV field isolates from 51 outpatient cases of Acute Respiratory Infectious Network (ARINET) and 54 inpatient cases of severe lower respiratory infection (SLRI) surveillance, in order to identify recombination in field samples. When analyzing parts of the 5'NCR and VP4/VP2 encoding sequences, we found intra- and interspecies recombinants in field strains of HRV-A and -C. Nineteen cases of recombination events (18.1%) were found among 105 field strains. For HRV-A, there were five cases (4.8%) of intraspecies recombination events and three cases (2.8%) of interspecies recombination events. For HRV-C, there were four cases (3.8%) of intraspecies recombination events and seven cases (6.7%) of interspecies recombination events. Recombination events were significantly more frequently observed in the ARINET samples (18 cases) than in the SLRI samples (1 case; P< 0.0001). The recombination breakpoints were located in nucleotides (nt) 472-554, which comprise stem-loop 5 in the internal ribosomal entry site (IRES), based on the HRV-B 35 sequence (accession no. FJ445187). Our findings regarding genomic recombination in circulating HRV-A and -C strains suggest that recombination might play a role in HRV fitness and could be a possible determinant of disease severity caused by various HRV infections in patients with ARI.
Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Humans; Infant; Middle Aged; Phylogeny; Picornaviridae Infections; Recombination, Genetic; Respiratory Tract Infections; Rhinovirus; Viral Proteins; Young Adult
PubMed: 23826363
DOI: 10.1371/journal.pone.0068081 -
The Pediatric Infectious Disease Journal Jun 2017Susceptibility to rhinovirus (RV)-induced early wheezing episode has been recognized as an important risk factor for asthma, but the data on different RV species are...
BACKGROUND
Susceptibility to rhinovirus (RV)-induced early wheezing episode has been recognized as an important risk factor for asthma, but the data on different RV species are limited. Our aim was to investigate the risk for recurrences in first-time wheezing children with special focus on RV species.
METHODS
First-time wheezing children (88 inpatients and 23 outpatients) were prospectively followed at 2-week, 2-month and 12-month time-points, and at first recurrence within 12 months. The respiratory virus etiology was analyzed using polymerase chain reaction. RV-positive samples were sequenced. The primary outcomes were time to a new physician-confirmed wheezing episode, time to a new RV-induced wheezing episode and time to the initiation of regular controller medication for asthma symptoms.
RESULTS
The median age of the children was 12 months (standard deviation, 6.0), 67% were males and 23% were sensitized. RV dominated in symptomatic and asymptomatic infections. Different RV strains were observed in 97% (67/69) of consecutive samples during follow-up. First-time wheezing children with RV-C and RV-A had an increased risk for a new physician-confirmed wheezing episode and a new RV-associated wheezing episode than non-RV group (all P < 0.05). Also, the risk for the initiation of regular controller medication was increased in RV-A and RV-C groups when compared with non-RV group (both P < 0.05).
CONCLUSIONS
RV causes reinfections with different strains in small children after the first wheezing episode. Both RV-A and RV-C affected children have an increased risk for recurrence, especially RV associated, and initiation of regular controller medication than those with other viruses.
Topics: Asymptomatic Infections; Female; Follow-Up Studies; Humans; Infant; Male; Picornaviridae Infections; Prospective Studies; Respiratory Sounds; Rhinovirus; Treatment Outcome
PubMed: 28027280
DOI: 10.1097/INF.0000000000001495 -
NatureRecently, Rossman et al. have described the three-dimensional structure of a human rhinovirus. A possible host cell surface receptor binding site was identified with a...
Recently, Rossman et al. have described the three-dimensional structure of a human rhinovirus. A possible host cell surface receptor binding site was identified with a cleft on each icosahedral face. Two highly conserved amino-acid sequences found in rhino-, polio-, and foot-and-mouth disease (FMD) viruses are located near the base of this site and could be important in maintaining its topology. We have prepared site-specific antibodies to two synthetic peptides which include these sequences. The antibodies bind to the predicted capsid proteins of rhinovirus and neutralize approximately 60% of 48 rhinovirus serotypes tested. These results could provide a route to a rhinovirus vaccine effective against most of the numerous serotypes of this virus.
Topics: Antibodies, Viral; Capsid; Epitopes; Immunosorbent Techniques; Molecular Weight; Neutralization Tests; Oligopeptides; Receptors, Virus; Rhinovirus; Species Specificity
PubMed: 2444889
DOI: 10.1038/329736a0 -
Brazilian Journal of Microbiology :... Mar 2021Human rhinovirus (HRV) is one of the most common human viral pathogens related to infections of the upper and lower respiratory tract, which can result in bronchiolitis...
INTRODUCTION
Human rhinovirus (HRV) is one of the most common human viral pathogens related to infections of the upper and lower respiratory tract, which can result in bronchiolitis and pneumonia. However, the relevance of HRV in human health was under-estimated for long time due to the absence of molecular targets for influenza and influenza-like syndrome surveillance in Brasília, Brazil.
OBJECTIVES
The main objective of this study was analyze the clinical characteristics and outcomes of HRV infections in comparison with patients without HRV and other common respiratory viruses.
MATERIALS AND METHODS
For this purpose, new specific primer sets were designed based on the high throughput sequencing analysis in previous study. These primers were used for HRV detection by RT-qPCR and Sanger sequencing of amplified cDNA of 5' genomic region. The phylogenetic tree with representative HRV isolates was constructed using the Mega X software. Statistical analysis considering the patient profiles were performed using IBM SPSS program with non-parametric tests.
RESULTS
The most prevalent virus in negative samples was rhinovirus (n = 40), including three rhinovirus species (rhinovirus A, B, and C). The odds ratio associated with HRV infection was 2.160 for patients younger than 2 years and 4.367 for people living in rural areas. The multiple analysis showed lower chance of patients with HRV presenting respiratory distress.
CONCLUSION
In this study, it was reported the predominance of rhinoviruses in cases of respiratory illness for negative patients for the influenza and influenza-like syndrome surveillance, being rhinorrhea, the most significant symptom associated with the disease.
Topics: Brazil; Child; Child, Preschool; Female; Humans; Male; Middle Aged; Phylogeny; Picornaviridae Infections; Respiratory Tract Infections; Rhinovirus; Viruses
PubMed: 33410102
DOI: 10.1007/s42770-020-00411-0 -
Viruses Mar 2024A less than one-month-old infant with symptoms of rhinitis died unexpectedly in his sleep. He was not born prematurely and had no known underlying disease. Cerebrospinal...
A less than one-month-old infant with symptoms of rhinitis died unexpectedly in his sleep. He was not born prematurely and had no known underlying disease. Cerebrospinal fluid, nasopharyngeal and lung samples, and rectal swab were found to be positive for subgroup A rhinovirus, while the blood was negative. This case highlights the important finding that the rhinovirus, a common pathogen associated with upper respiratory tract infections, can sometimes, as the only pathogen, lead to complications such as a cerebrospinal infection and be involved in the sudden infant death syndrome (SIDS). Vigilance is necessary in case of viral infections in the infant's environment, and measures of hygiene and protection must be encouraged in order to reduce the risk of the SIDS.
Topics: Humans; Sudden Infant Death; Picornaviridae Infections; Rhinovirus; Male; Infant; Respiratory Tract Infections; Infant, Newborn
PubMed: 38675861
DOI: 10.3390/v16040518 -
The Pediatric Infectious Disease Journal Mar 2019In this analysis of 2 prospective multicenter, multi-year cohorts of children hospitalized for bronchiolitis in the United States and Finland, 306 rhinovirus infections...
In this analysis of 2 prospective multicenter, multi-year cohorts of children hospitalized for bronchiolitis in the United States and Finland, 306 rhinovirus infections were genotyped. Rhinovirus-A and -C species were predominant in the US study, while rhinovirus-C species was predominant in the Finland study. In both cohorts, there were no significant between-species differences in clinical characteristics, including acute severity measures.
Topics: Bronchiolitis, Viral; Female; Finland; Hospitalization; Humans; Infant; Male; Molecular Typing; Picornaviridae Infections; Prospective Studies; Rhinovirus; Severity of Illness Index; United States
PubMed: 30001231
DOI: 10.1097/INF.0000000000002141